— Surveillance data suggest a viral etiology, including enteroviruses

Acute flaccid myelitis (AFM) appears to have a viral etiology, but exactly which virus is causing the polio-like illness remains unknown, according to an analysis of pediatric cases reported to the CDC from 2015 to 2017.

Among 193 children with confirmed AFM, 79% reported a respiratory or febrile illness from 2 to 7 days before limb weakness set in, and the cases tended to cluster in the late summer or fall, reported Tracy Ayers, PhD, of the CDC in Atlanta, Georgia, and colleagues.

Although no single pathogen was identified as the driving force behind these cases, viral pathogens were found in almost half of patients (47%), with coxsackievirus A16 detected in the cerebrospinal fluid and serum of one patient and enterovirus D68 -- the most predominant pathogen detected in the 2014 outbreak -- detected in serum of another, they wrote in Pediatrics.

Together, these findings "strongly suggest a viral etiology, including [enteroviruses]," the authors stated.

AFM, a rare condition characterized by acute onset of focal limb weakness and spinal cord gray matter lesions, was classified as such during the 2014 outbreak, in which 120 individuals contracted the disorder from August through December of that year.

AFM made national news in 2018, with a total of 228 confirmed cases in 41 U.S. states, and four confirmed cases in 2019. The spike in reported cases in 2018 was so dramatic that the CDC announced they would start tracking AFM cases.

Importantly, 143 cases (74%) in this study occurred in 2016, "fitting within the larger epidemiological context of a biennial pattern of AFM outbreaks in the U.S. documented from 2014 to 2018," wrote Samuel Dominguez, MD, PhD, of Children's Hospital Colorado in Aurora, and colleagues, in an accompanying commentary.

However, myelitis in the grey matter of the spinal cord has been associated with poliovirus, non-polio enteroviruses, flaviviruses, and autoantibody conditions, Dominguez and colleagues noted.

"As such, a single etiology to explain all cases of the clinical syndrome of AFM at all times would not be expected," they wrote.

Although enterovirus D68 appears to be the most likely driving force behind AFM, widespread enterovirus circulation makes it difficult to establish a causal relationship when collected from nonsterile sites, the authors reported.

"Serologic evidence of widespread infection with EV-D68, even before the first notable increase of AFM in 2014, suggests that if EV-D68 was the primary cause of AFM in 2014 and 2016, other factors must play a role in the development of this rare outcome," they wrote.

AFM outbreaks need to be analyzed separately from the "background noise" of endemic AFM, Dominguez's group wrote. Developing intrathecal enterovirus antibody tests for cerebrospinal fluid could also improve the ability to diagnose cases, they added.

All cases in this analysis were confirmed to be AFM by an expert panel of pediatricians and neurologists. The CDC requested sterile site and nonsterile-site specimens from each of the patients with confirmed AFM, which were tested for poliovirus, enteroviruses, rhinoviruses, and parechoviruses.

Overall, 305 incidents were reported from 43 states, of which 193 pediatric cases were confirmed. Children tended to be white (53%) and male (61%) with a median age of 6 years.

Across the 3-year study period, the majority of cases occurred from August through November (61%). In 2016 when the number of cases peaked, 88% of cases occurred from August through November, the authors reported.

At the time of limb weakness onset, one-third of patients had cranial nerve findings (33%), quadriplegia (36%), or required mechanical ventilation (33%), the authors reported. Over one-quarter presented with an altered mental status at this time (28%).

Poliovirus was not detected in any cases, and enterovirus D68 was found in about one-quarter of confirmed cases from 2015 through 2017 (24%), although it was also found in patients with misclassified AFM.

In CDC laboratories, 32 of 90 children with upper respiratory specimens were positive for enterovirus and rhinovirus (36%) and 15 of 77 kids with stool samples were positive for enterovirus and rhinovirus (19%), the authors reported.

Also, in non-CDC laboratories, 61 of 151 children who had respiratory specimens tested were positive for enterovirus and rhinovirus (46%) and 22 of 78 patients with stool samples were positive for enterovirus and rhinovirus (52%), they added.

The number of cases to be reported in the study period across the U.S. could be underestimated as AFM is not a nationally notifiable condition, and has a range of clinical severity, the authors reported. Also, enterovirus surveillance is limited by geographic variability and an inability to determine type-specific trends by year, they added.

"Enhanced AFM surveillance with focused analysis of distinct signals from outbreak periods is essential to targeting the development of speciﬁc therapeutics and preventive vaccines to combat this potentially devastating neurologic condition," according to Dominguez and colleagues.

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